The present invention relates to 5'-amino acid esters of ribavirin represented by formula I: ##STR3##
pharmaceutical compositions containing them as well as methods of treating patients having susceptible viral infections, e.g., chronic hepatitis C infections by administering a therapeutically effective amount of an amino acid ester of ribavirin represented by formula I, alone, or in combination with a therapeutically effective amount of interferon-alpha.
Chronic infection with hepatitis C virus ("HCV") is an insidious and slow-progressing disease having a significant impact on the quality of life. It can eventually result in cirrhosis of the liver, decompensated liver disease and/or hepatocelluar carcinoma.
Combination treatment with interferon alfa-2b and ribavirin of patients with chronic hepatitis C is disclosed by Reichard et al.(The Lancet 1998; 351;83-87; and T. Poynard et al.( The Lancet, 1998, Vol. 352, Oct. 31, p 1426-1432). See also J. G. McHutchinson et al. (N. Engl. J. Med.,1998, 339:1485-1492); and G. L. Davis et al. (N. Engl. J. Med., 1998, 339:1493-1499). However, this combination therapy is not always effective due to side effects associated ribavirin such as ribavirin-related hemolysis, and anemia.
There is a definite need for more potent, safer ribavirin derivatives having fewer side effects for use as monotherapy or in combination with antiviral agents, e.g., interferon-alpha, to treat patients having susceptible viral infections, e.g., chronic hepatitis C infections, in a long-term, effective manner.